Korean guidelines for the management of gout Jennifer Jooha Lee; Ji Soo Lee; Min Kyung Chung ...
The Korean journal of internal medicine,
09/2023, Letnik:
38, Številka:
5
Journal Article
Recenzirano
Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management ...during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
Sixteen monthly air–sea heat flux products from global ocean/coupled reanalyses are compared over 1993–2009 as part of the Ocean Reanalysis Intercomparison Project (ORA-IP). Objectives include ...assessing the global heat closure, the consistency of temporal variability, comparison with other flux products, and documenting errors against in situ flux measurements at a number of OceanSITES moorings. The ensemble of 16 ORA-IP flux estimates has a global positive bias over 1993–2009 of 4.2 ± 1.1 W m
−2
. Residual heat gain (i.e., surface flux + assimilation increments) is reduced to a small positive imbalance (typically, +1–2 W m
−2
). This compensation between surface fluxes and assimilation increments is concentrated in the upper 100 m. Implied steady meridional heat transports also improve by including assimilation sources, except near the equator. The ensemble spread in surface heat fluxes is dominated by turbulent fluxes (>40 W m
−2
over the western boundary currents). The mean seasonal cycle is highly consistent, with variability between products mostly <10 W m
−2
. The interannual variability has consistent signal-to-noise ratio (~2) throughout the equatorial Pacific, reflecting ENSO variability. Comparisons at tropical buoy sites (10°S–15°N) over 2007–2009 showed too little ocean heat gain (i.e., flux into the ocean) in ORA-IP (up to 1/3 smaller than buoy measurements) primarily due to latent heat flux errors in ORA-IP. Comparisons with the Stratus buoy (20°S, 85°W) over a longer period, 2001–2009, also show the ORA-IP ensemble has 16 W m
−2
smaller net heat gain, nearly all of which is due to too much latent cooling caused by differences in surface winds imposed in ORA-IP.
This qualitative study explores how individuals recently experiencing abortions feel about donating fetal tissue for research. In addition, we sought to identify motivating or discouraging factors ...that influence decision making for these individuals.
We recruited individuals living in Hawaii who reported undergoing an abortion in the previous 6 months for one-on-one semi-structured interviews as part of a broader study investigating views on peri-abortion research practices and protections. We devoted approximately 15 minutes of each 1-hour interview to discussing the donation of aborted fetal tissue for research. We double coded transcribed interviews and identified themes related to fetal tissue donation.
We interviewed 25 respondents and identified 4 themes. (1) Individuals viewed fetal tissue donation as an opportunity to help others. (2) Respondents preferred for aborted fetal tissue to be used rather than discarded. (3) Respondents viewed the fetal tissue to be an extension of themselves, so informed consent is critical. (4) Information found online promotes mistrust of fetal tissue handling.
Individuals who have had an abortion are open to fetal tissue donation for research purposes. Pre-abortion counseling could be improved by clarifying the process of fetal tissue handling and, when available, discussing options for fetal tissue donation.
Informed pregnant individuals who have had an abortion appear to be supportive of fetal tissue research and their views can differ from the concerns of ethicists, politicians, and scientists. The perspective of the individuals donating fetal tissue should be included in future discussions of fetal tissue research.
Mutation and aberrant expression of apoptotic proteins are hallmarks of cancer. These changes prevent proapoptotic signals from being transmitted to executioner caspases, thereby averting apoptotic ...death and allowing cellular proliferation. Caspase-3 is the key executioner caspase, and it exists as an inactive zymogen that is activated by upstream signals. Notably, concentrations of procaspase-3 in certain cancerous cells are significantly higher than those in noncancerous controls. Here we report the identification of a small molecule (PAC-1) that directly activates procaspase-3 to caspase-3 in vitro and induces apoptosis in cancerous cells isolated from primary colon tumors in a manner directly proportional to the concentration of procaspase-3 inside these cells. We found that PAC-1 retarded the growth of tumors in three different mouse models of cancer, including two models in which PAC-1 was administered orally. PAC-1 is the first small molecule known to directly activate procaspase-3 to caspase-3, a transformation that allows induction of apoptosis even in cells that have defective apoptotic machinery. The direct activation of executioner caspases is an anticancer strategy that may prove beneficial in treating the many cancers in which procaspase-3 concentrations are elevated.
The aim of this study was to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) support.
...LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid.
Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC.
There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio OR: 1.3, 95% confidence interval CI: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75).
The HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process.
• Premise of the study: Interspecific reproductive barriers (IRBs) act to ensure species integrity by preventing hybridization. Previous studies on interspecific crosses in the tomato clade have ...focused on the success of fruit and seed set. The SI × SC rule (SI species × SC species crosses are incompatible, but the reciprocal crosses are compatible) often applies to interspecific crosses. Because SI systems in the Solanaceae affect pollen tube growth, we focused on this process in a comprehensive study of interspecific crosses in the tomato clade to test whether the SI × SC rule was always followed. • Methods: Pollen tube growth was assessed in reciprocal crosses between all 13 species of the tomato clade using fluorescence microscopy. • Key results: In crosses between SC and SI species, pollen tube growth follows the SI × SC rule: interspecific pollen tube rejection occurs when SI species are pollinated by SC species, but in the reciprocal crosses (SC × SI), pollen tubes reach ovaries. However, pollen tube rejection occurred in some crosses between pairs of SC species, demonstrating that a fully functional SI system is not necessary for pollen tube rejection in interspecific crosses. Further, gradations in the strength of both pistil and pollen IRBs were revealed in interspecific crosses using SC populations of generally SI species. • Conclusion: The SI × SC rule explains many of the compatibility relations in the tomato clade, but exceptions occur with more recently evolved SC species and accessions, revealing differences in strength of both pistil and pollen IRBs.
Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for ...patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors.
We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers.
We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors.
This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.
Data are limited on temporal trends in outcomes of hospitalization and surgery in pediatric Crohn's disease (CD) and ulcerative colitis (UC). Thus, we evaluated the U.S. nationwide temporal trends ...for incidence of hospitalization and intestinal resection along with associated resource utilization.
We used the Kids' Inpatient Database (1997, 2000, 2003, 2006, and 2009) to identify all admissions for children aged 18 years or younger with a primary CD (International Classification of Diseases, Ninth Revision ICD-9: 555.X) or UC (ICD-9: 556.X) diagnosis or a secondary CD or UC diagnosis and procedural code of intestinal resection. Poisson regression analysis was performed to evaluate time trends in the incidence of hospitalization, intestinal resection, and hospital resource utilization.
The annual incidence of hospitalization was 5.7 and 3.5 per 100,000 children for CD and UC, respectively, with significant increases over time for CD (annual percent increase API, 3.8%; 95% confidence interval CI, 3.0%-4.5%) and UC (API, 4.5%; 95% CI, 4.3%-4.7%). Median hospital days per hospitalization for CD and UC remained stable, whereas median charge per hospitalization increased for CD (API, 4.1%; 95% CI, 2.6%-5.6%) and UC (API, 4.7%; 95% CI, 3.5%-5.9%). The annual incidence of intestinal resection remained stable for UC at 0.6 per 100,000 children but climbed for CD (API, 2.1%; 95% CI, 0.1-4.2).
The annual incidence of hospitalization is climbing in pediatric inflammatory bowel diseases, accompanied by rising intestinal resection rates for CD and stable colectomy rates for UC. With escalating resource utilization, the economic and health burden of pediatric inflammatory bowel diseases is substantial.
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